keyword
MENU ▼
Read by QxMD icon Read
search

nmdar inhibition

keyword
https://www.readbyqxmd.com/read/28098256/dopamine-promotes-nmda-receptor-hypofunction-in-the-retina-through-d1-receptor-mediated-csk-activation-src-inhibition-and-decrease-of-glun2b-phosphorylation
#1
Renato Socodato, Felipe N Santiago, Camila C Portugal, Ivan Domith, Thaísa G Encarnação, Erick C Loiola, Ana L M Ventura, Marcelo Cossenza, João B Relvas, Newton G Castro, Roberto Paes-de-Carvalho
Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D1 receptors (D1Rs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between D1Rs, Src and NMDARs in retinal neurons. We reveal that dopamine-mediated D1R stimulation provoked NMDAR hypofunction in retinal neurons by attenuating NMDA-gated currents, by preventing NMDA-elicited calcium mobilization and by decreasing the phosphorylation of NMDAR subunit GluN2B...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089695/the-pharmacology-of-tacrine-at-n-methyl-d-aspartate-receptors
#2
REVIEW
Martin Horak, Kristina Holubova, Eugenie Nepovimova, Jan Krusek, Martina Kaniakova, Jan Korabecny, Ladislav Vyklicky, Kamil Kuca, Ales Stuchlik, Jan Ricny, Karel Vales, Ondrej Soukup
The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully understood. It has been reported to involve a wide spectrum of targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. Here, we review the effect of tacrine and its derivatives on the NMDA receptors (NMDAR) with a focus on the mechanism of action and biological consequences related to the Alzheimer's disease treatment. Our findings indicate that effect of tacrine on glutamatergic neurons is both direct and indirect...
January 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28069922/mechanisms-of-nmda-receptor-and-voltage-gated-l-type-calcium-channel-dependent-hippocampal-ltp-critically-rely-on-proteolysis-that-is-mediated-by-distinct-metalloproteinases
#3
Grzegorz Wiera, Daria Nowak, Inge Van Hove, Piotr Dziegiel, Lieve Moons, Jerzy W Mozrzymas
: Long-term potentiation (LTP) is widely perceived as a memory substrate and in the hippocampal CA3-CA1 pathway, distinct forms of LTP depend on N-methyl-D-aspartate (NMDA) receptors (nmdaLTP) or L-type voltage-gated calcium channels (vdccLTP). Long-term potentiation is also known to be effectively regulated by extracellular proteolysis that is mediated by various enzymes. Herein, we investigated whether in mice hippocampal slices these distinct forms of LTP are specifically regulated by different metalloproteinases (MMPs)...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28065779/effects-of-panax-notoginseng-ginsenoside-rb1-on-abnormal-hippocampal-microenvironment-in-rats
#4
Shiyun Wang, Minghong Li, Ying Guo, Chen Li, Lanou Wu, Xin-Fu Zhou, Yaohui Luo, Dong An, Shude Li, Haiyun Luo, Lijin Pu
: Cerebral ischemia damages central neurons, and abnormal microenvironment in ischemic condition is the key factor to the damages. The increase of local concentration of glutamic acid, the overload of Ca(2+), and the mitochondrial stress caused by release of cytochrome C are important factors of abnormal microenvironment in cerebral ischemia. In this study ginsenoside Rb1, a compound from Panax Notoginseng, was used to intervene abnormal environment of neurons in the hippocampal CA1 region in two animal models (microperfusion model and photothrombosis model)...
January 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28045032/mechanical-stress-activates-nmda-receptors-in-the-absence-of-agonists
#5
Mohammad Mehdi Maneshi, Bruce Maki, Radhakrishnan Gnanasambandam, Sophie Belin, Gabriela K Popescu, Frederick Sachs, Susan Z Hua
While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca(2+) entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca(2+) influx...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032990/iterative-focused-screening-with-biological-fingerprints-identifies-selective-asc-1-inhibitors-distinct-from-traditional-high-throughput-screening
#6
Peter S Kutchukian, Lee Warren, Brian C Magliaro, Adam Amoss, Jason A Cassaday, Gregory O'Donnell, Brian Squadroni, Paul Zuck, Danette Pascarella, J Chris Culberson, Andrew J Cooke, Danielle Hurzy, Kelly-Ann Sondra Schlegel, Fiona Thomson, Eric N Johnson, Victor N Uebele, Jeffrey D Hermes, Sophie Parmentier-Batteur, Michael Finley
N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer's disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine-serine-cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs...
January 6, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/27999123/early-alterations-of-hippocampal-neuronal-firing-induced-by-abeta42
#7
Daniela Gavello, Chiara Calorio, Claudio Franchino, Federico Cesano, Valentina Carabelli, Emilio Carbone, Andrea Marcantoni
We studied the effect of Amyloid β 1-42 oligomers (Abeta42) on Ca(2+) dependent excitability profile of hippocampal neurons. Abeta42 is one of the Amyloid beta peptides produced by the proteolytic processing of the amyloid precursor protein and participates in the initiating event triggering the progressive dismantling of synapses and neuronal circuits. Our experiments on cultured hippocampal network reveal that Abeta42 increases intracellular Ca(2+) concentration by 46% and inhibits firing discharge by 19%...
December 19, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27981829/discerning-the-role-of-the-hydroxyproline-residue-in-the-structure-of-conantokin-rl-b-and-its-role-in-glun2b-subunit-selective-antagonistic-activity-toward-n-methyl-d-aspartate-receptors
#8
Yue Yuan, Rashna D Balsara, Jaroslav Zajicek, Shailaja Kunda, Francis J Castellino
Conantokins (con) are short γ-carboxyglutamate (Gla)-containing polypeptides expressed by marine snails that function as antagonists of N-methyl-d-aspartate receptor (NMDAR) ion channels. The Gla residues govern structural conformations and antagonistic activities of the conantokins. In addition to Gla, some conantokins, e.g., conRl-B, also contain a hydroxyproline (HyP or O) residue, which in this case is centrally located in the peptide at position 10. Because conRl-B specifically inhibits ion channels of GluN2B subunit-containing heterotetrameric NMDARs, we evaluated the unusual role of HyP(10) in this effect...
December 27, 2016: Biochemistry
https://www.readbyqxmd.com/read/27976681/amphetamine-and-methamphetamine-increase-nmdar-glun2b-synaptic-currents-in-midbrain-dopamine-neurons
#9
Ming-Hua Li, Suzanne M Underhill, Cheryl Reed, Tamara J Phillips, Susan G Amara, Susan L Ingram
The psychostimulants amphetamine (AMPH) and methamphetamine (MA) are widely abused illicit drugs. Here we show that both psychostimulants acutely increase NMDA receptor (NMDAR)-mediated synaptic currents and decrease AMPA receptor (AMPAR)/NMDAR ratios in midbrain dopamine neurons. The potentiation depends on the transport of AMPH into the cell by the dopamine transporter. NMDAR-GluN2B receptor inhibitors, ifenprodil, RO 25-6981, and RO 04-5595, inhibit the potentiation without affecting basal-evoked NMDA currents, indicating that NMDAR-GluN2B receptors are activated by AMPH...
January 18, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27975343/need-for-better-diabetes-treatment-the-therapeutic-potential-of-nmda-receptor-antagonists
#10
A Welters, E Lammert, E Mayatepek, T Meissner
Diabetes mellitus is the most common metabolic disorder in children and adolescents. Optimal control of blood glucose concentration is essential to prevent acute and diabetic long-term complications. The options to treat diabetes have clearly improved over the last decades, however, to date neither type 1 diabetes nor type 2 diabetes mellitus can be cured. Therefore, diabetes research aims at developing β-cell protective agents that prevent or even reverse diabetes onset. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system (CNS) where they hold central roles in CNS function...
December 14, 2016: Klinische Pädiatrie
https://www.readbyqxmd.com/read/27940363/evidence-for-presynaptically-silent-synapses-in-the-immature-hippocampus
#11
Jae Young Yoon, Sukwoo Choi
Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27930673/dopamine-neurons-change-the-type-of-excitability-in-response-to-stimuli
#12
Ekaterina O Morozova, Denis Zakharov, Boris S Gutkin, Christopher C Lapish, Alexey Kuznetsov
The dynamics of neuronal excitability determine the neuron's response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#13
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27922130/the-nmda-receptor-glun2c-subunit-controls-cortical-excitatory-inhibitory-balance-neuronal-oscillations-and-cognitive-function
#14
Subhash C Gupta, Aparna Ravikrishnan, Jinxu Liu, Zhihao Mao, Ratnamala Pavuluri, Brandon G Hillman, Pauravi J Gandhi, Dustin J Stairs, Ming Li, Rajesh R Ugale, Daniel T Monaghan, Shashank M Dravid
Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2C-containing NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27874976/etidronate-rescues-cognitive-deficits-through-improving-synaptic-transmission-and-suppressing-apoptosis-in-2-vessel-occlusion-model-rats
#15
Wen Li, Huijuan Yuan, Yao Yu, Yuen-Ki Cheong, Guogang Ren, Zhuo Yang
Vascular dementia is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (ET) showed neuroprotective effects against glutamate-injured PC12 cells. Thus, in this study, we aimed to observe the effects of ET on learning and memory impairment and the related mechanism in 2-vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce vascular dementia model...
November 22, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27866902/the-atypical-antipsychotic-olanzapine-disturbs-depotentiation-by-modulating-machrs-and-impairs-reversal-learning
#16
Woo Seok Song, Jin Hee Cha, Sang Ho Yoon, Young Seon Cho, Kyeong-Yeol Park, Myoung-Hwan Kim
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27865768/regulation-of-extrasynaptic-signaling-by-polysialylated-ncam-impact-for-synaptic-plasticity-and-cognitive-functions
#17
REVIEW
Hristo Varbanov, Alexander Dityatev
The activation of synaptic N-methyl-d-aspartate-receptors (NMDARs) is crucial for induction of synaptic plasticity and supports cell survival, whereas activation of extrasynaptic NMDARs inhibits long-term potentiation and triggers neurodegeneration. A soluble polysialylated form of the neural cell adhesion molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B-containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism result in impaired synaptic plasticity and learning, which could be repaired by reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or downstream signaling through RasGRF1 and p38 MAP kinase...
November 16, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27862359/the-conversion-of-glutamate-by-glutamine-synthase-in-neocortical-astrocytes-from-juvenile-rat-is-important-to-limit-glutamate-spillover-and-peri-extrasynaptic-activation-of-nmda-receptors
#18
Yosra Trabelsi, Mohamed Amri, Hélène Becq, Florence Molinari, Laurent Aniksztejn
Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na(+) and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation...
February 2017: Glia
https://www.readbyqxmd.com/read/27859797/in-vitro-and-in%C3%A2-vivo-effects-of-a-novel-dimeric-inhibitor-of-psd-95-on-excitotoxicity-and-functional-recovery-after-experimental-traumatic-brain-injury
#19
Jens Bak Sommer, Anders Bach, Hana Malá, Kristian Strømgaard, Jesper Mogensen, Darryl S Pickering
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a novel dimeric inhibitor of PSD-95, UCCB01-147, on histopathology and long-term cognitive outcome after controlled cortical impact (CCI) in rats. As excitotoxic cell death is thought to be a prominent part of the pathophysiology of TBI, we also investigated the neuroprotective effects of UCCB01-147 and related compounds on NMDA-induced cell death in cultured cortical neurons...
January 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27852777/amyloid-%C3%AE-peptide-nitrotyrosination-stabilizes-oligomers-and-enhances-nmdar-mediated-toxicity
#20
Biuse Guivernau, Jaume Bonet, Victòria Valls-Comamala, Mònica Bosch-Morató, Juan A Godoy, Nibaldo C Inestrosa, Alex Perálvarez-Marín, Xavier Fernández-Busquets, David Andreu, Baldomero Oliva, Francisco J Muñoz
: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the pathological aggregation of the amyloid-β peptide (Aβ). Monomeric soluble Aβ can switch from helicoidal to β-sheet conformation, promoting its assembly into oligomers and subsequently to amyloid fibrils. Oligomers are highly toxic to neurons and have been reported to induce synaptic transmission impairments. The progression from oligomers to fibrils forming senile plaques is currently considered a protective mechanism to avoid the presence of the highly toxic oligomers...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
keyword
keyword
99566
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"